Heteroaroylhydrazide derivatives of monocyclic beta-lactam antibiotics

Compounds of the formula ##STR39## and pharmaceutically acceptable salts thereof, wherein R.sub.1 and R.sub.2 are the same or different and each is hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, phenyl, substituted phenyl or a 4, 5, 6 or 7-membered heterocycle or one of R.sub.1 and R.sub.2 is hydrogen and the other is azido, halomethyl, dihalomethyl, trihalomethyl, alkoxycarbonyl, --CH.sub.2 X.sub.1 ;

• wherein X.sub.1 is azido, amino, hydroxy, carboxy, alkoxycarbonyl, alkanoylamino, phenylcarbonylamino, (substituted phenyl)carbonylamino, alkylsulfonyloxy, phenylsulfonyloxy, (substituted phenyl)sulfonyloxy, phenyl, substituted phenyl, cyano, ##STR40## --S--X.sub.2, or --O--X.sub.2 (wherein A, X.sub.2, X.sub.6 and X.sub.7 are as hereinafter defined);
• --S--X.sub.2 or --O--X.sub.2 ;
• wherein X.sub.2 is alkyl, substituted alkyl, phenyl, substituted phenyl, phenylalkyl, (substituted phenyl)alkyl,alkanoyl, substituted alkanoyl, phenylalkanoyl, (substituted phenyl)alkanoyl, phenylcarbonyl, (substituted phenyl)carbonyl, or heteroarylcarbonyl;
• and in the case of when X.sub.1 is --O--X.sub.2 then X.sub.2 can also be alkylideneamino, alkanoylamino, carboxyalkylideneamino, alkylsulphonylamino, alkoxycarbonylalkylsulphonylamino or N,N-cyclodialkanoylamino, ##STR41## wherein one of X.sub.3 and X.sub.4 is hydrogen and the other is hydrogen or alkyl, or X.sub.3 and X.sub.4 when taken together with the carbon atom to which they are attached form a cycloalkyl groups, and X.sub.5 is formyl, alkanoyl, phenylcarbonyl, (substituted phenyl)carbonyl, phenylalkylcarbonyl, (substituted phenyl)alkylcarbonyl, carboxyl, alkoxycarbonyl, aminocarbonyl, (substituted amino)carbonyl, or cyano, or ##STR42## wherein A is --CH.dbd.CH--, --(CH.sub.2).sub.m --, --(CH.sub.2).sub.m --O--, --(CH.sub.2).sub.m --NH--, or --CH.sub.2 --S--CH.sub.2 --, m is 0, 1 or 2, and X.sub.6 and X.sub.7 are the same or different and each is hydrogen, alkyl, phenyl or substituted pheny, or X.sub.6 is hydrogen and X.sub.7 is amino, substituted amino, alkanoylamino or alkoxy, or X.sub.6 and X.sub.7 when taken together with the nitrogen atom to which they are attached form a 4, 5, 6 or 7-membered heterocycle;
• R.sub.3 and R.sub.4 are the same or different and each is hydrogen or alkyl or R.sub.3 and R.sub.4 taken together with the carbon atom to which they are attached are cycloalkyl;
• R.sub.5 and R.sub.6 are the same or different and each is hydrogen or alkyl or R.sub.5 and R.sub.6 taken together with the nitrogen atoms to which they are attached form a 1,2-diazacylobutane, 1,2-diazacyclopentane, 1,2-diacyclohexane, or 1,2-diazacycloheptane ring;
• R.sub.7 is hydrogen, fluorine, chlorine or bromine;
• X is a nitrogen atom or CH;
• Y is a nitrogen atom or CH;
• provided that either X or Y is always a nitrogen atom.
• wherein the term "substituted alkyl" refers to alkyl groups substituted with azido, amino, halogen, hydroxy, carboxy, cyano, alkoxycarbonyl, aminocarbonyl, alkanoyloxy, alkoxy, phenyloxy, (substituted phenyl)oxy, mercapto, alkylthio, phenylthio, (substituted phenyl)thio, alkylsulfinyl or alkylsulfonyl groups;
• the term "substituted phenyl" refers to a phenyl group substituted with 1, 2 or 3 amino, halogen, hydroxyl, trifluoromethyl, alkyl of 1 to 4 carbon atoms, alkoxy of 1 to 4 carbon atoms, alkanoyloxy, aminocarbonyl, or carboxy groups;
• the term "substituted amino" refers to a group having the formula --NX.sub.8 X.sub.9 wherein X.sub.8 is hydrogen, alkyl, phenyl, substituted phenyl, phenylalkyl or (substituted phenyl)alkyl, and X.sub.9 is alkyl, phenyl, substituted phenyl, phenylakyl, (substitutedphenyl)alkyl, hydroxy, cyano, alkoxy, phenylalkoxy or amino;
• the term "heteroaryl" refers to pyridinyl, furanyl, pyrrolyl, thienyl, 1,2,3-triazolyl, 1,2,4-triazolyl, imdazolyl, thiazolyl, thiadiazolyl, pyrimidinyl, oxazolyl, triazinyl, teterazol, tetrazolyl or one of the above groups substituted with one or more halogen, hydroxy, nitro,amino, cyano, trifluoromethyl, alkyl of 1 to 4 carbon atoms, alkoxy of 1 to 4 carbon atoms, alkylsulfonyl, phenyl, substituted phenyl, 2-furfurylideneamino, benzylideneamino, or substituted alkyl wherein the alkyl group has 1 to 4 carbon atoms, groups;
• the term "a 4,5,6 or 7-membered heterocycle" refers to pyridinyl, furanyl, pyrrolyl, thienyl, 1,2,3-triazolyl, 1,2,4-triazolyl, imidazolyl, thiazolyl, thiadiazolyl, pyrimidinyl, oxazolyl, triazinyl, tetrazolyl, azetinyl, oxetanyl, thietanyl, piperidinyl, piperazinyl, imidazolylidinyl, oxazolidinyl, pyrrolidinyl, tetrahydropyrimidinyl, dihydrothiazolyl or hexahydroazepinyl or one of the above groups substituted with one or more oxo, halogen, hydroxy, nitro, amino, cyano, trifluoromethyl, alkyl of 1 to 4 carbon atoms, alkoxy of 1 to 4 carbon atoms, alkylsulfonyl, phenyl, substituted phenyl, 2-furfurylideneamino, benzylideneamino, or substituted alkyl wherein the alkyl groups has 1 to 4 carbon atom, groups.